The number of diseases found to be caused by defects of the mitochondrial genome has grown significantly over the last decade (Wallace et al., 1988; Holt et al., 1988; Harding et al., 1999; Papa et al., 1996; Wallace, 1999 and Pulkes et al., 2001). Organs affected by defects in the mitochondrial DNA (mtDNA) include the brain, skeletal muscle, heart, kidney and liver (De Vivo, 1993). Hence, neuromuscular and neurodegenerative diseases represent the two largest groups of mtDNA diseases. Also, prominent clinical signs often involve the visual system. Ptosis, restriction of eye movement, optic atrophy, pigmentary retinopathy, sudden or subacute visual loss, and hemianopia are particularly noteworthy (De Vivo, 1993). (See also www.neuro.wustl.edu/neuromuscular/mitosyn.html or www.gen.emory.edu/mitomap.html.) Despite major advances in understanding mtDNA defects at the genetic and biochemical level, however, there is no satisfactory treatment available for the vast majority of patients. This is due to the fact that any mtDNA mutation or deletion affects the final common pathway of oxidative metabolism in the mitochondria making it impossible to bypass the defect by administering alternative energy-carrying metabolites (Chrzanowska-Lightowler et al., 1995). These objective limitations of conventional biochemical treatment for patients with defects of mtDNA warrant the exploration of other gene therapeutic approaches.